RESUMO
Two previously undescribed caryophyllane-related sesquiterpenoids, antipacids A (1) and B (2), with a novel bicyclo[5.2.0] core skeleton, and known compound clovane-2ß,9α-diol (3), along with rumphellolide L (4), an esterified product of 1 and 3, were isolated from the organic extract of octocoral Rumphella antipathes. Their structures, including the absolute configurations were elucidated by spectroscopic and chemical experiments. In vivo anti-inflammatory activity analysis indicated that antipacid B (2) inhibited the generation of superoxide anions and the release of elastase by human neutrophils, with IC50 values of 11.22 and 23.53 µM, respectively, while rumphellolide L (4) suppressed the release of elastase with an IC50 value of 7.63 µM.
Assuntos
Antozoários/metabolismo , Anti-Inflamatórios/farmacologia , Neutrófilos/efeitos dos fármacos , Sesquiterpenos Policíclicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Humanos , Elastase de Leucócito/metabolismo , Estrutura Molecular , Neutrófilos/metabolismo , Sesquiterpenos Policíclicos/isolamento & purificação , Relação Estrutura-Atividade , Superóxidos/metabolismoRESUMO
Integrating multifactor blood analysis is a key step toward a precise diagnosis of the health status of marine mammals. Variations in the circulating lipid profile reflect changes in the metabolism and physiology of an individual. To demonstrate the practicability of lipid profiling for physiological assessment, the phosphorylcholine-containing lipids in the plasma of long-term managed beluga whales (Delphinapterus leucas) were profiled using a lipidomics methodology. Using a multivariate analysis, the mean corpuscular volume, cholesterol, potassium, and γ-glutamyltranspeptidase levels were well modeled with the lipid profile of the female whales. In the models, the correlated lipids provided information about blood parameter-related metabolism and physiological regulation, in particular relating to cholesterol and inflammation. In the males, the levels of cholesterol, triglycerides, blood urea nitrogen, creatinine, plasma iron, and segmented neutrophil were well modeled with the lipid profile. In addition to providing information about the related metabolism and regulation, through a cross-linked analysis of the blood parameters, the correlated lipids indicated a parallel regulation involved in the energy metabolism of the male whales. Lipidomics as a method for revealing the context of physiological change shows practical potential for the health care of managed whales.
Assuntos
Criação de Animais Domésticos/métodos , Animais de Zoológico , Metabolismo dos Lipídeos/fisiologia , Lipídeos/análise , Baleias/fisiologia , Animais , Lipídeos/genéticaRESUMO
A known norcembranoidal diterpene, 5-episinuleptolide (1), along with a new analogue, 4α-hydroxy-5-episinuleptolide (2), were isolated from a cultured-type soft coral Sinularia numerosa. The structures of 1 and 2 were elucidated on the basis of spectroscopic methods and by comparison of the data with those of the related metabolites. Cytotoxicity of metabolites 1 and 2 against a panel of tumor cells is also described. Compound 2 exhibited moderate cytotoxicity toward CCRF-CEM cells with an IC50 value 4.21 µg/mL. Preliminary SAR (structure activity relationship) information was obtained from these two compounds.
Assuntos
Antozoários/química , Diterpenos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
BACKGROUND: The burst size of a phage is important prior to phage therapy and probiotic usage. The efficiency for a phage to burst its host bacterium can result from molecular domino effects of the phage gene expressions which dominate to control host machinery after infection. We found two Podoviridae phages, ÏA318 and ÏAs51, burst a common host V. alginolyticus with different efficiencies of 72 and 10 PFU/bacterium, respectively. Presumably, the genome sequences can be compared to explain their differences in burst sizes. RESULTS: Among genes in 42.5 kb genomes with a GC content of 43.5%, 16 out of 47 open-reading frames (ORFs) were annotated to known functions, including RNA polymerase (RNAP) and phage structure proteins. 11 strong phage promoters and three terminators were found. The consensus sequence for the new vibriophage promoters is AATAAAGTTGCCCTATA, where the AGTTG bases of -8 through -12 are important for the vibriophage specificity, especially a consensus T at -9 position eliminating RNAP of K1E, T7 and SP6 phages to transcribe the genes. ÏA318 and ÏAs51 RNAP shared their own specific promoters. In comparing ÏAs51 with ÏA318 genomes, only two nucleotides were deleted in the RNAP gene and three mutating nucleotides were found in the major capsid genes. CONCLUSION: Subtle analyses on the residue alterations uncovered the effects of five nucleotide mutations on the functions of the RNAP and capsid proteins, which account for the host-bursting efficiency. The deletion of two nucleotides in RNAP gene truncates the primary translation due to early stop codon, while a second translational peptide starting from GTG just at deletion point can remediate the polymerase activity. Out of three nucleotide mutations in major capsid gene, H53N mutation weakens the subunit assembly between capsomeres for the phage head; E313K reduces the fold binding between ß-sheet and Spine Helix inside the peptide.
Assuntos
Bacteriófagos/genética , Proteínas do Capsídeo/genética , RNA Polimerases Dirigidas por DNA/genética , Mutação Puntual , Vibrio alginolyticus/virologia , Sequência de Aminoácidos , Bacteriófagos/enzimologia , Sequência de Bases , Genoma Viral , Especificidade de Hospedeiro , Anotação de Sequência Molecular , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Análise de Sequência de DNA , Liberação de VírusRESUMO
Five new 7α-hydroxyeunicellin-based diterpenoids, designated as cladieunicellins M-Q (1-5), were isolated from a Formosan octocoral Cladiella sp. The structures of 1-5 were elucidated on the basis of spectroscopic methods and by comparison of the data with those of the related metabolites. Cytotoxicity of metabolites 1-5 against the human leukemia Molt 4 and HL 60 is also described. Among them, compounds 1, 3 and 5 exhibited moderate cytotoxicity toward Molt 4 cells with IC50 values 16.43, 14.17 and 15.55 µM, respectively. Preliminary SAR (structure activity relationship) information was obtained from these compounds and their analogues.
Assuntos
Antozoários/metabolismo , Antineoplásicos/farmacologia , Diterpenos/farmacologia , Leucemia/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Células HL-60 , Humanos , Concentração Inibidora 50 , Leucemia/patologia , Análise Espectral , Relação Estrutura-AtividadeRESUMO
A novel sesquiterpenoid, rumphellaoic acid A (1), was isolated from the gorgonian coral Rumphella antipathies, and was found to possess a carbon skeleton that was obtained for the first time from a natural sources. The structure of 1 was elucidated by spectroscopic methods and this compound and was found to exert a moderate inhibitory effect on the release of elastase by human neutrophils.
Assuntos
Antozoários/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Animais , Humanos , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/metabolismo , Análise Espectral/métodos , TaiwanRESUMO
Two novel diterpenoids, sinularbols A (1) and B (2), which were found to possess a new carbon skeleton were isolated from the soft coral Sinularia arborea. The structures of compounds 1 and 2 were elucidated by spectroscopic methods and 2 displayed a moderately inhibitory effect on the generation of superoxide anion by human neutrophils.
Assuntos
Antozoários/química , Diterpenos/química , Animais , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Superóxidos/químicaRESUMO
The structures, names, bioactivities and references of 138 briarane-type diterpenoids, including 87 new compounds, are summarized in this review. All the briarane-type compounds mentioned in this review article were obtained from gorgonian corals including the genus Briareum, Dichotella, Junceella and Verrucella. Some of these compounds showed potential bioactivities.
Assuntos
Antozoários/metabolismo , Diterpenos/isolamento & purificação , Animais , Diterpenos/química , Diterpenos/farmacologia , HumanosRESUMO
Three new 8-alkylcoumarins, 7-O-methylphellodenol-B (1), 7-methoxy-8-(3-methyl- 2,3-epoxy-1-oxobutyl)chromen-2-one (2), and 3'-O-methylvaginol (3), together with seven known compounds (4-10) were isolated from the fruits of Cnidium monnieri. Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. All the isolates were evaluated the cytoprotective activity by MTS cell proliferation assay and the results showed that all the three new 8-alkylcoumarins exhibited cytoprotective effect on Neuro-2a neuroblastoma cells injured by hydrogen peroxide.
Assuntos
Apiaceae/química , Cumarínicos/farmacologia , Frutas/química , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Neuroblastoma/patologia , Oxidantes/toxicidade , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologiaRESUMO
Two new marine-derived caryophyllene-type sesquiterpenoids, rumphellols A and B (1 and 2), were obtained from the gorgonian coral, Rumphella antipathies, collected off the waters of Taiwan. Although caryophyllene-type sesquiterpenes are rarely found in marine organisms, compounds of this type could be principal components of R. antipathies. The structures of new Compounds 1 and 2 were determined by analysis of their spectroscopic data, including 1D and 2D NMR experiments. Caryophyllene 1 and 2 were evaluated in terms of their anti-inflammatory activity by examining their inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.
Assuntos
Antozoários/química , Anti-Inflamatórios não Esteroides/química , Extratos Celulares/química , Sesquiterpenos/química , Sesterterpenos/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Extratos Celulares/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Elastase Pancreática/metabolismo , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacologia , Sesterterpenos/farmacologia , Superóxidos/metabolismoRESUMO
Wild bitter gourd (Momordica charantia L. var. abbreviate Seringe), a common vegetable in Asia, is used in traditional medicine to treat various diseases, including inflammation. Extant literature indicates that wild bitter gourds have components that activate PPARα and PPARγ. This research probed the influence of adding wild bitter gourd to diets on inflammation responses in mice with sepsis induced by intraperitoneal injection of LPS. Male BALB/c mice were divided normal, sepsis, positive control, and three experimental groups. The latter ate diets with low (1%), moderate (2%), and high (10%) ratios of wild bitter gourd lyophilized powder. Before mice were sacrificed, with the exception of the normal group, intraperitoneal injection of LPS induced sepsis in each group; positive control group was injected with LPS after PDTC. This experiment revealed starkly lower weights in groups with added wild bitter gourd than those of the remaining groups. Blood lipids (TG, cholesterol, and NEFA) were also lower in comparison to the sepsis group, and blood glucose concentrations recovered and approached normal levels. Blood biochemistry values related to inflammation reactions indicated GOT, GPT, C-RP, and NO concentrations of groups with added wild bitter gourd were all lower than those of the sepsis group. Secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α tallied significantly lower in comparison to the sepsis group, whereas secretion levels of IL-10 anti-inflammatory cytokine increased. Expression level of proteins NF-κB, iNOS, and COX-2 were significantly inhibited. Results indicate wild bitter gourd in diets promoted lipid metabolism, reducing fat accumulation, and improving low blood glucose in sepsis. Addition of wild bitter gourd can reduce inflammation biochemical markers or indicators and pro-inflammatory cytokines in the body, hence improving the inflammation responses in mice with sepsis.
Assuntos
Anti-Inflamatórios/farmacologia , Momordica charantia/química , Extratos Vegetais/farmacologia , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Mediadores da Inflamação/sangue , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Extratos Vegetais/uso terapêutico , Sepse/sangue , Sepse/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismoRESUMO
Two new 4,5-seco-caryophyllane sesquiterpenoids, rumphellaones B (1) and C (2), which were found to possess unprecedented γ-lactone moieties, were obtained from the gorgonian coral Rumphella antipathies. The structures of 1 and 2 were elucidated by spectroscopic methods and compound 2 was found to display modest inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils at a concentration of 10 µg/mL.
Assuntos
Antozoários/química , Anti-Inflamatórios/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Células Cultivadas , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Elastase Pancreática/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Superóxidos/metabolismoRESUMO
Two new 13-hydroxycembrane diterpenoids, arbolides A (1) and B (2), along with a known trihydroxysteroid, crassarosterol A (3), were isolated from the soft coral Sinularia arborea. The structures of new cembranes 1 and 2 were elucidated by spectroscopic methods. Steroid 3 was found to exhibit cytotoxicity toward K562 and MOLT-4 leukemia.
Assuntos
Antozoários/química , Antozoários/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Células K562 , Leucemia/tratamento farmacológicoRESUMO
A new norcembranoidal diterpene, 1-epi-sinulanorcembranolide A (1), and a new cembranoidal diterpene, flexibilin D (2), were isolated from the soft corals, Sinularia gaweli and Sinularia flexibilis, respectively. The structures of new metabolites 1 and 2 were elucidated by spectroscopic methods, and compound 2 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In addition, S. flexibilis yielded a known cembrane, 5-dehydrosinulariolide (3); the structure, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Diterpenos/química , Diterpenos/isolamento & purificação , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Análise Espectral , Difração de Raios XRESUMO
Three new cembrane-type diterpenoids, flexibilins A-C (1-3), along with a known cembrane, (-)-sandensolide (4), were isolated from the soft coral, Sinularia flexibilis. The structures of cembranes 1-4 were elucidated by spectroscopic methods. The structure of 4, including its absolute stereochemistry, was further confirmed by single-crystal X-ray diffraction analysis. Cembrane 2 displayed a moderate inhibitory effect on the release of elastase by human neutrophils.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/efeitos dos fármacos , Animais , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Análise Espectral , Taiwan , Difração de Raios XRESUMO
A new quinone derivative, flexibilisquinone (1), was isolated from the cultured soft coral Sinularia flexibilis, originally distributed in the waters of Taiwan. The structure of quinone 1 was established by extensive spectroscopic methods, particularly 1D and 2D NMR experiments. In the in vitro anti-inflammatory effects test, quinone 1 was found to significantly inhibit the accumulation of the pro-inflammatory iNOS and COX-2 proteins of the LPS-stimulated RAW264.7 macrophage cells.
Assuntos
Antozoários/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Quinonas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Linhagem Celular , Ciclo-Oxigenase 2/efeitos dos fármacos , Inflamação/induzido quimicamente , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Quinonas/químicaRESUMO
The widespread use of hexabromocyclododecane (HBCD), a brominated flame retardant, is a major public health concern because of the toxic, persistent, and bioaccumulative nature of HBCD. However, there is limited information available regarding the distribution and transportation of HBCD in sediments across various environmental settings, spanning from riverine to marine environments in the Kaohsiung area of Taiwan. In this study, we comprehensively investigated the level and distribution of and potential ecological risk posed by HBCD in surface sediments in the Kaohsiung area of Taiwan. In sediment samples from stations on the Love River and Kaohsiung Port area, the concentrations of HBCD ranged from 10.6 to 320.1 µg/kg dry weight (dw) and nondetectable (n.d.) to 58.4 µg/kg dw, respectively. The concentrations of HBCD in sediment collected from the M1, M2, and M3 sites, located in the Cijin coastal area, were 896.2 µg/kg dw, 3.2 µg/kg dw (
Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Poluentes Químicos da Água , Taiwan , Monitoramento Ambiental , Hidrocarbonetos Bromados/análise , Sedimentos Geológicos , Rios , Retardadores de Chama/análise , Poluentes Químicos da Água/análiseRESUMO
A fast reversed-phase liquid chromatography-electrospray ionization triple quadrupole mass spectrometry method was developed for the molecular species profiling of glycerophosphocholine (GPC) and sphingomyelin (SM) in total lipid extracts. A two-stage mass spectrometry strategy was adopted to analyze in detail the composition of lipid molecular species. Precursor ion analysis was first conducted to obtain the preliminary composition profile of the phosphorylcholine-containing lipid. The product ion spectra were sequentially acquired for each recorded signal to determine the molecular structure of the lipid. A total of 150 GPCs and 12 SMs were identified in the fetal mouse lung with relative amounts ranging from 13.7% to less than 0.002% (normalizing by the total signal response). A column packed with core-shell particles was used to obtain excellent chromatographic separation with a shorter time demand in a conventional high-performance liquid chromatography system. Considering the compromise between the chromatographic efficiency and the electrospray signal response, the optimization of the mobile phase improves the chromatographic plate number to approximately 40,000 and the detection limits to less than 0.001 mg/L. The applicability of the method was validated through a study of chemically induced early lung maturation. The metabolic alteration in the fetal mouse lung was clearly reflected in the GPC and SM composition with several characteristics of the molecular structure that related to the character of the phospholipid layer upon the epithelial lining of alveoli and the relevant cell function. The results indicated that this analytical strategy is reliable for comprehensive molecular species profiling of GPC and SM and might be extended to the analysis of other phospholipids.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Pulmão/química , Pulmão/embriologia , Fosforilcolina/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Esfingomielinas/análise , Animais , Feminino , Limite de Detecção , Lipídeos/análise , Camundongos , Espectrometria de Massas em Tandem/métodosRESUMO
A new labdane-type diterpenoid, echinolabdane A (1), and a new sterol, 6-epi-yonarasterol B (2), were isolated from a gorgonian coral identified as Echinomuricea sp. The structures of metabolites 1 and 2 were elucidated by spectroscopic methods. Echinolabdane A (1) possesses a novel tetracyclic skeleton with an oxepane ring jointed to an α,ß-unsaturated-γ-lactone ring by a hemiketal moiety, and this compound is the first labdane-type diterpenoid to be obtained from marine organisms belonging to the phylum Cnidaria. 6-epi-Yonarasterol B (2) is the first steroid derivative to be isolated from gorgonian coral belonging to the genus Echinomuricea, and this compound displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.
Assuntos
Antozoários/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Animais , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Cnidários/química , Diterpenos/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/antagonistas & inibidores , Elastase Pancreática/metabolismo , Análise Espectral/métodos , Esteróis/química , Esteróis/isolamento & purificação , Esteróis/farmacologia , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismoRESUMO
A new halimane-type diterpenoid, echinohalimane A (1), was isolated from a gorgonian, identified as Echinomuricea sp. The structure of 1 was determined by spectroscopic methods and this compound was found to exhibit cytotoxicity toward various tumor cells and display an inhibitory effect on the release of elastase by human neutrophils. Echinohalimane A (1) is the first halimane analogue from the marine organisms belonging to phylum Cnidaria.